2-[3-Cyano-4-(2-methyl-prop-oxy)phen-yl]-4-methyl-thia-zole-5-carboxylic acid pyridine solvate.

In the title compound, C(16)H(16)N(2)O(3)S·C(5)H(5)N, the benzene and thia-zole rings of the Febuxostat [2-(3-cyano-4-isobut-yloxy)phenyl-4-methyl-5-thia-zolecarboxylic acid] mol-ecule are almost coplanar [dihedral angle = 2.4 (1)°]. The carboxyl group is coplanar with the thia-zole ring [O-C-C-C and O-C-C-S torsion angles of -0.7 (4) and 0.6 (3)°, respectively]. The pyridine mol-ecule of crystallization is linked to the Febuxostat mol-ecule through an O-H⋯N hydrogen bond. A weak π-π stacking inter-action is observed between the benzene ring of the Febuxostat mol-ecule and pyridine mol-ecule, with a centroid-centroid distance of 3.7530 (18) Å.

Related literature

For general background to gout, see: Alexander (2008 ▶). For the synthesis, polymorphism, stability and biological activity of Febuxostat, see: Edwards (2009 ▶); Hiramatsu et al. (2000 ▶); Perez-Ruiz et al. (2008 ▶); Sorbera et al. (2001 ▶); Zhou et al. (2007 ▶). For a related structure, see: Fontrodona et al. (2001 ▶).

Experimental

Crystal data

C16H16N2O3S·C5H5N

M = 395.47

Triclinic,

a = 8.6040 (17) Å

b = 10.339 (2) Å

c = 12.611 (3) Å

α = 82.51 (3)°

β = 80.69 (3)°

γ = 69.61 (3)°

V = 1034.4 (4) Å3

Z = 2

Mo Kα radiation

μ = 0.18 mm−1

T = 296 K

0.30 × 0.20 × 0.20 mm

Data collection

Enraf–Nonius CAD-4 diffractometer

Absorption correction: ψ scan (North et al., 1968 ▶) T min = 0.947, T max = 0.964

4017 measured reflections

3747 independent reflections

2815 reflections with I > 2σ(I)

R int = 0.032

3 standard reflections every 200 reflections intensity decay: 1%

Refinement

R[F 2 > 2σ(F 2)] = 0.049

wR(F 2) = 0.156

S = 0.99

3747 reflections

255 parameters

H-atom parameters constrained

Δρmax = 0.33 e Å−3

Δρmin = −0.19 e Å−3

Data collection: CAD-4 EXPRESS (Enraf–Nonius, 1994 ▶); cell refinement: CAD-4 EXPRESS; data reduction: XCAD4 (Harms & Wocadlo,1995 ▶); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXL97.

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809039002/ci2885sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809039002/ci2885Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

C16H16N2O3S·C5H5N	Z = 2
Mr = 395.47	F(000) = 416
Triclinic, P1	Dx = 1.270 Mg m−3
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 8.6040 (17) Å	Cell parameters from 25 reflections
b = 10.339 (2) Å	θ = 10–13°
c = 12.611 (3) Å	µ = 0.18 mm−1
α = 82.51 (3)°	T = 296 K
β = 80.69 (3)°	Block, brown
γ = 69.61 (3)°	0.30 × 0.20 × 0.20 mm
V = 1034.4 (4) Å3

Enraf–Nonius CAD-4 diffractometer	2815 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.032
graphite	θmax = 25.3°, θmin = 1.6°
ω/2θ scans	h = 0→10
Absorption correction: ψ scan (North et al., 1968)	k = −11→12
Tmin = 0.947, Tmax = 0.964	l = −14→15
4017 measured reflections	3 standard reflections every 200 reflections
3747 independent reflections	intensity decay: 1%

Refinement on F2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.049	H-atom parameters constrained
wR(F2) = 0.156	w = 1/[σ2(Fo2) + (0.1P)2 + 0.12P] where P = (Fo2 + 2Fc2)/3
S = 0.99	(Δ/σ)max = 0.001
3747 reflections	Δρmax = 0.33 e Å−3
255 parameters	Δρmin = −0.19 e Å−3
0 restraints	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.030 (5)

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

	x	y	z	Uiso*/Ueq
S	0.83182 (8)	0.26459 (7)	0.30078 (4)	0.0564 (2)
O1	0.5471 (2)	0.2112 (2)	0.10983 (14)	0.0754 (6)
O2	0.7344 (2)	0.3198 (2)	0.08925 (14)	0.0754 (6)
H2A	0.7091	0.3381	0.0277	0.113*
O3	1.1361 (2)	0.20514 (18)	0.76698 (12)	0.0586 (5)
N1	0.6870 (3)	0.1219 (2)	0.43509 (15)	0.0586 (5)
N2	1.2786 (4)	0.4042 (4)	0.5613 (2)	0.1041 (10)
C1	0.6483 (3)	0.2464 (3)	0.14487 (19)	0.0570 (6)
C2	0.6882 (3)	0.2095 (3)	0.25744 (18)	0.0523 (6)
C3	0.7976 (3)	0.1847 (2)	0.42631 (17)	0.0510 (6)
C4	0.6240 (3)	0.1354 (3)	0.33987 (18)	0.0562 (6)
C5	0.4943 (4)	0.0713 (3)	0.3353 (2)	0.0790 (9)
H5A	0.4167	0.1282	0.2874	0.118*
H5B	0.4357	0.0636	0.4062	0.118*
H5C	0.5472	−0.0191	0.3096	0.118*
C6	0.8868 (3)	0.1864 (2)	0.51606 (17)	0.0509 (6)
C7	0.9984 (3)	0.2585 (3)	0.50346 (18)	0.0554 (6)
H7A	1.0183	0.3054	0.4374	0.067*
C8	1.0807 (3)	0.2614 (2)	0.58894 (17)	0.0529 (6)
C9	1.0521 (3)	0.1928 (2)	0.68921 (17)	0.0494 (5)
C10	0.9425 (3)	0.1192 (2)	0.70122 (17)	0.0539 (6)
H10A	0.9230	0.0714	0.7669	0.065*
C11	0.8622 (3)	0.1166 (3)	0.61544 (18)	0.0555 (6)
H11A	0.7892	0.0664	0.6247	0.067*
C12	1.1917 (4)	0.3398 (3)	0.57499 (19)	0.0705 (8)
C13	1.1139 (3)	0.1363 (3)	0.87244 (17)	0.0532 (6)
H13A	1.1489	0.0371	0.8677	0.064*
H13B	0.9971	0.1684	0.9025	0.064*
C14	1.2185 (3)	0.1690 (3)	0.94322 (18)	0.0555 (6)
H14A	1.3341	0.1432	0.9081	0.067*
C15	1.1568 (4)	0.3222 (3)	0.9600 (2)	0.0716 (7)
H15A	1.1603	0.3744	0.8914	0.107*
H15B	1.2270	0.3404	1.0039	0.107*
H15C	1.0440	0.3487	0.9952	0.107*
C16	1.2148 (4)	0.0832 (4)	1.0511 (2)	0.0829 (9)
H16A	1.2555	−0.0134	1.0389	0.124*
H16B	1.1021	0.1077	1.0865	0.124*
H16C	1.2844	0.1012	1.0956	0.124*
N3	0.6706 (3)	0.3879 (3)	0.89010 (17)	0.0662 (6)
C17	0.5872 (4)	0.4524 (3)	0.6832 (2)	0.0784 (9)
H17A	0.5589	0.4742	0.6134	0.094*
C18	0.6965 (4)	0.5024 (3)	0.7160 (2)	0.0755 (8)
H18A	0.7444	0.5589	0.6687	0.091*
C19	0.7359 (4)	0.4686 (3)	0.8200 (2)	0.0702 (7)
H19A	0.8106	0.5035	0.8418	0.084*
C20	0.5646 (3)	0.3398 (3)	0.8567 (2)	0.0743 (8)
H20A	0.5182	0.2830	0.9048	0.089*
C21	0.5200 (4)	0.3700 (4)	0.7544 (2)	0.0816 (9)
H21A	0.4447	0.3345	0.7341	0.098*

	U11	U22	U33	U12	U13	U23
S	0.0649 (4)	0.0694 (4)	0.0399 (3)	−0.0261 (3)	−0.0190 (3)	0.0038 (3)
O1	0.0859 (13)	0.1005 (15)	0.0542 (11)	−0.0423 (11)	−0.0318 (9)	0.0028 (10)
O2	0.0786 (12)	0.1131 (16)	0.0442 (9)	−0.0428 (12)	−0.0256 (9)	0.0128 (10)
O3	0.0751 (11)	0.0709 (11)	0.0383 (8)	−0.0323 (9)	−0.0229 (7)	0.0072 (7)
N1	0.0607 (12)	0.0784 (14)	0.0422 (10)	−0.0284 (11)	−0.0138 (9)	−0.0006 (9)
N2	0.148 (3)	0.140 (3)	0.0683 (16)	−0.102 (2)	−0.0507 (17)	0.0359 (16)
C1	0.0562 (14)	0.0680 (16)	0.0436 (12)	−0.0115 (12)	−0.0179 (11)	−0.0042 (11)
C2	0.0498 (13)	0.0645 (15)	0.0428 (12)	−0.0140 (11)	−0.0157 (10)	−0.0078 (10)
C3	0.0547 (13)	0.0588 (14)	0.0387 (12)	−0.0158 (11)	−0.0124 (10)	−0.0011 (10)
C4	0.0553 (14)	0.0725 (16)	0.0445 (12)	−0.0224 (12)	−0.0131 (10)	−0.0058 (11)
C5	0.0804 (19)	0.113 (2)	0.0605 (16)	−0.0508 (18)	−0.0194 (14)	−0.0009 (16)
C6	0.0562 (13)	0.0583 (14)	0.0383 (11)	−0.0164 (11)	−0.0130 (10)	−0.0027 (10)
C7	0.0665 (15)	0.0631 (15)	0.0382 (11)	−0.0226 (12)	−0.0155 (10)	0.0049 (10)
C8	0.0653 (15)	0.0591 (14)	0.0391 (12)	−0.0249 (12)	−0.0163 (10)	0.0034 (10)
C9	0.0599 (13)	0.0503 (13)	0.0378 (11)	−0.0152 (11)	−0.0148 (10)	−0.0015 (9)
C10	0.0697 (15)	0.0583 (14)	0.0362 (11)	−0.0240 (12)	−0.0147 (10)	0.0053 (10)
C11	0.0658 (15)	0.0625 (15)	0.0448 (12)	−0.0273 (12)	−0.0150 (10)	−0.0011 (10)
C12	0.095 (2)	0.089 (2)	0.0439 (13)	−0.0501 (17)	−0.0309 (13)	0.0172 (13)
C13	0.0673 (15)	0.0578 (14)	0.0367 (11)	−0.0214 (12)	−0.0164 (10)	0.0025 (10)
C14	0.0565 (14)	0.0710 (16)	0.0400 (12)	−0.0198 (12)	−0.0142 (10)	−0.0021 (11)
C15	0.0767 (18)	0.084 (2)	0.0662 (16)	−0.0361 (15)	−0.0154 (14)	−0.0125 (14)
C16	0.104 (2)	0.103 (2)	0.0470 (14)	−0.0364 (19)	−0.0328 (15)	0.0091 (14)
N3	0.0607 (13)	0.0864 (16)	0.0445 (11)	−0.0141 (12)	−0.0165 (10)	0.0022 (10)
C17	0.0798 (19)	0.094 (2)	0.0447 (14)	−0.0046 (17)	−0.0231 (13)	0.0020 (14)
C18	0.085 (2)	0.0775 (19)	0.0538 (15)	−0.0176 (16)	−0.0115 (14)	0.0084 (13)
C19	0.0737 (17)	0.0765 (18)	0.0588 (16)	−0.0207 (15)	−0.0166 (13)	−0.0022 (13)
C20	0.0643 (17)	0.104 (2)	0.0547 (15)	−0.0288 (16)	−0.0183 (13)	0.0081 (14)
C21	0.0717 (18)	0.118 (3)	0.0588 (16)	−0.0306 (17)	−0.0282 (14)	0.0032 (16)

S—C2	1.714 (2)	C10—H10A	0.93
S—C3	1.718 (2)	C11—H11A	0.93
O1—C1	1.214 (3)	C13—C14	1.508 (3)
O2—C1	1.304 (3)	C13—H13A	0.97
O2—H2A	0.82	C13—H13B	0.97
O3—C9	1.352 (3)	C14—C15	1.516 (4)
O3—C13	1.442 (3)	C14—C16	1.526 (4)
N1—C3	1.310 (3)	C14—H14A	0.98
N1—C4	1.367 (3)	C15—H15A	0.96
N2—C12	1.143 (4)	C15—H15B	0.96
C1—C2	1.485 (3)	C15—H15C	0.96
C2—C4	1.369 (4)	C16—H16A	0.96
C3—C6	1.472 (3)	C16—H16B	0.96
C4—C5	1.494 (3)	C16—H16C	0.96
C5—H5A	0.96	N3—C20	1.323 (4)
C5—H5B	0.96	N3—C19	1.330 (4)
C5—H5C	0.96	C17—C18	1.357 (4)
C6—C11	1.386 (3)	C17—C21	1.357 (5)
C6—C7	1.386 (3)	C17—H17A	0.93
C7—C8	1.391 (3)	C18—C19	1.377 (4)
C7—H7A	0.93	C18—H18A	0.93
C8—C9	1.396 (3)	C19—H19A	0.93
C8—C12	1.432 (4)	C20—C21	1.371 (4)
C9—C10	1.384 (3)	C20—H20A	0.93
C10—C11	1.382 (3)	C21—H21A	0.93
C2—S—C3	89.34 (11)	O3—C13—C14	107.94 (19)
C1—O2—H2A	109.5	O3—C13—H13A	110.1
C9—O3—C13	118.94 (18)	C14—C13—H13A	110.1
C3—N1—C4	111.2 (2)	O3—C13—H13B	110.1
O1—C1—O2	124.6 (2)	C14—C13—H13B	110.1
O1—C1—C2	123.2 (3)	H13A—C13—H13B	108.4
O2—C1—C2	112.2 (2)	C13—C14—C15	111.3 (2)
C4—C2—C1	129.7 (2)	C13—C14—C16	109.1 (2)
C4—C2—S	110.16 (17)	C15—C14—C16	110.7 (2)
C1—C2—S	120.2 (2)	C13—C14—H14A	108.6
N1—C3—C6	123.1 (2)	C15—C14—H14A	108.6
N1—C3—S	114.60 (16)	C16—C14—H14A	108.6
C6—C3—S	122.33 (18)	C14—C15—H15A	109.5
N1—C4—C2	114.7 (2)	C14—C15—H15B	109.5
N1—C4—C5	118.6 (2)	H15A—C15—H15B	109.5
C2—C4—C5	126.7 (2)	C14—C15—H15C	109.5
C4—C5—H5A	109.5	H15A—C15—H15C	109.5
C4—C5—H5B	109.5	H15B—C15—H15C	109.5
H5A—C5—H5B	109.5	C14—C16—H16A	109.5
C4—C5—H5C	109.5	C14—C16—H16B	109.5
H5A—C5—H5C	109.5	H16A—C16—H16B	109.5
H5B—C5—H5C	109.5	C14—C16—H16C	109.5
C11—C6—C7	117.9 (2)	H16A—C16—H16C	109.5
C11—C6—C3	121.4 (2)	H16B—C16—H16C	109.5
C7—C6—C3	120.7 (2)	C20—N3—C19	117.5 (2)
C6—C7—C8	120.5 (2)	C18—C17—C21	118.6 (3)
C6—C7—H7A	119.8	C18—C17—H17A	120.7
C8—C7—H7A	119.8	C21—C17—H17A	120.7
C7—C8—C9	120.9 (2)	C17—C18—C19	119.4 (3)
C7—C8—C12	119.5 (2)	C17—C18—H18A	120.3
C9—C8—C12	119.6 (2)	C19—C18—H18A	120.3
O3—C9—C10	125.7 (2)	N3—C19—C18	122.2 (3)
O3—C9—C8	115.8 (2)	N3—C19—H19A	118.9
C10—C9—C8	118.6 (2)	C18—C19—H19A	118.9
C11—C10—C9	119.9 (2)	N3—C20—C21	123.0 (3)
C11—C10—H10A	120.0	N3—C20—H20A	118.5
C9—C10—H10A	120.0	C21—C20—H20A	118.5
C10—C11—C6	122.2 (2)	C17—C21—C20	119.2 (3)
C10—C11—H11A	118.9	C17—C21—H21A	120.4
C6—C11—H11A	118.9	C20—C21—H21A	120.4
N2—C12—C8	178.1 (3)
O1—C1—C2—C4	−0.7 (4)	C6—C7—C8—C9	−0.4 (4)
O2—C1—C2—C4	179.4 (2)	C6—C7—C8—C12	−178.2 (2)
O1—C1—C2—S	−179.5 (2)	C13—O3—C9—C10	0.5 (3)
O2—C1—C2—S	0.6 (3)	C13—O3—C9—C8	−179.5 (2)
C3—S—C2—C4	0.17 (19)	C7—C8—C9—O3	−178.6 (2)
C3—S—C2—C1	179.2 (2)	C12—C8—C9—O3	−0.8 (4)
C4—N1—C3—C6	−179.6 (2)	C7—C8—C9—C10	1.4 (4)
C4—N1—C3—S	0.1 (3)	C12—C8—C9—C10	179.1 (2)
C2—S—C3—N1	−0.1 (2)	O3—C9—C10—C11	178.9 (2)
C2—S—C3—C6	179.5 (2)	C8—C9—C10—C11	−1.0 (3)
C3—N1—C4—C2	0.1 (3)	C9—C10—C11—C6	−0.2 (4)
C3—N1—C4—C5	−179.3 (2)	C7—C6—C11—C10	1.1 (4)
C1—C2—C4—N1	−179.0 (2)	C3—C6—C11—C10	−178.8 (2)
S—C2—C4—N1	−0.2 (3)	C9—O3—C13—C14	−179.00 (19)
C1—C2—C4—C5	0.3 (4)	O3—C13—C14—C15	64.7 (3)
S—C2—C4—C5	179.2 (2)	O3—C13—C14—C16	−173.0 (2)
N1—C3—C6—C11	2.2 (4)	C21—C17—C18—C19	−0.1 (5)
S—C3—C6—C11	−177.39 (18)	C20—N3—C19—C18	0.0 (4)
N1—C3—C6—C7	−177.7 (2)	C17—C18—C19—N3	0.2 (4)
S—C3—C6—C7	2.7 (3)	C19—N3—C20—C21	−0.2 (4)
C11—C6—C7—C8	−0.8 (4)	C18—C17—C21—C20	−0.1 (5)
C3—C6—C7—C8	179.1 (2)	N3—C20—C21—C17	0.2 (5)

D—H···A	D—H	H···A	D···A	D—H···A
O2—H2A···N3i	0.82	1.79	2.611 (3)	174
C5—H5A···O1	0.96	2.52	3.055 (3)	115

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O2—H2A⋯N3i	0.82	1.79	2.611 (3)	174

Symmetry code: (i) .